The mRNA profile of postmortem brain shows evidence of neural signatures in certain psychiatric disorders such as bipolar disorder, major depression, schizophrenia, and other neuropsychiatric disorders. This suggests that diagnostic specificity might be present in the reported neural signatures. The neural signature could be further examined using peripheral lymphocytes as a neural probe. The broad goal of this application is to test for biomarkers and stability in postmortem brain using gene expression profiling by microarray. Aims 1 through 4 incorporate novel approaches to fill in existing gaps in scientific knowledge using an accessible tissue source of lymphocytes for a neural probe and organotypic brain culture as an extension to current postmortem studies to study candidate biomarkers. The present scientific gaps will be addressed in: Aim 1. Compare gene expression profiles in post-mortem human brain and outpatient lymphocyte tissue between controls, major depressive disorder (MDD), and bipolar disorder (BPD) groups for unique gene profiles that may act as diagnostic biomarkers for these disorders greatly facilitating better treatments. Aim 2. Simultaneous gene expression from brain and lymphocyte within the same subjects and analysis of lymphocyte expression between controls, MDD, and BPD subjects. Aim 3. Comparison between 2 sources of lymphocytes (outpatient and post-mortem) and effects of transformation on gene expression profiling. Aim 4. Stability testing of potential biomarkers using organotypic brain tissue culture to study the impact of agonal factors on mRNA profiling and biomarkers. The 4 aims of this application are inter-related, i.e. biomarker evaluation and the potential impact of agonal factors on the stability of biomarkers in peripheral and central gene expression. The potential use of biomarkers in lymphocytes will provide clinical researchers a tool to better address questions concerning diagnostic subgroups and treatment responders and non-responders.